What is emphysema, its etiology, clinical presentation, diagnostic criteria, and treatment recommendations?

Emphysema: Definition, Pathophysiology, and Clinical Management

Definition and Core Pathophysiology

Emphysema is a permanent destructive enlargement of airspaces distal to the terminal bronchioles without obvious fibrosis, resulting in loss of lung elastic recoil and destruction of alveolar attachments that cause airways to collapse during expiration. 1

• Emphysema represents the parenchymal destruction component of COPD, distinct from the airway disease component 1
• The destruction involves loss of alveolar walls and reduction in total lung gas exchange area 2
• This pathological process is slowly progressive and largely irreversible 1

Etiology

Cigarette smoking is the predominant cause of emphysema, with smokers prone to develop centriacinar emphysema where respiratory bronchioles, alveolar ducts, and alveoli at the center of the acinus are destroyed. 3

• Alpha-1 antitrypsin deficiency causes panacinar emphysema, where the entire acinus is destroyed 3
• The underlying mechanism involves protease-antiprotease imbalance when smoking-induced neutrophil elastase release inadequately inhibited 4
• Increased oxidative stress, programmed cell death, autophagy, and impaired repair mechanisms contribute to tissue destruction 5

Types of Emphysema

Three major patterns exist with distinct functional consequences 1, 6:

• Centriacinar (centrilobular) emphysema: Destroys respiratory bronchioles, alveolar ducts, and central alveoli while surrounding alveoli remain intact; associated with more small airways disease and less loss of elastic recoil for any level of respiratory function 3, 6
• Panacinar emphysema: Involves destruction of the entire acinus; associated with greater loss of elastic recoil that may appear early in disease development 1
• Paraseptal emphysema: Occurs close to connective tissue septae, leading to blebs on lung surface predisposing to pneumothorax or giant bullae 3

Clinical Presentation

Emphysema-dominant patients characteristically present with less prominent cough and sputum production compared to airway-dominant COPD. 7

• Progressive dyspnea on exertion is the hallmark symptom 7
• Hyperinflation manifests as increased anterior-posterior chest diameter 3
• Some patients exhibit symptoms suggesting airway hyperresponsiveness including cough and wheezing, though bronchodilator reversibility is usually moderate 3
• Advanced disease presents with arterial hypoxemia and potential pulmonary hypertension 3

Diagnostic Criteria

Spirometry and Pulmonary Function Testing

Full lung function testing including spirometry, static lung volumes, arterial blood gas analysis, and gas transfer should be assessed at baseline to document physiologic status. 3

• The key diagnostic feature is airflow obstruction (reduced FEV1/FVC ratio) that cannot be fully reversed 7
• Lower diffusing capacity (DLCO) due to alveolar destruction characterizes emphysema-dominant patients 7
• Static lung volume measurement documents the degree of hyperinflation 7
• Follow-up should include spirometry at yearly intervals 3

Imaging

High-resolution CT (HRCT) with quantitative analysis is the gold standard for phenotyping emphysema and is more sensitive than plain chest radiography or pulmonary function tests. 7, 8

• On HRCT, emphysema appears as areas of abnormally low attenuation (–600 to –800 Hounsfield units) contrasted with surrounding normal lung parenchyma 3
• In alpha-1 antitrypsin deficiency, classic finding is panacinar emphysema with uniform abnormally low attenuation and predominant lower lobe distribution 3
• Chest radiography in early disease is usually normal; advanced disease shows hyperinflation, increased radiolucency (particularly lower lung segments), flat diaphragms, and decreased vascular markings 3
• CT lung density is the most sensitive endpoint for disease progression, followed by TLCO, FEV1, and residual volume 2

Treatment Recommendations

Essential First-Line Intervention

Smoking cessation must be the highest priority intervention for all patients with emphysema, as it is the only measure proven to slow the accelerated decline in lung function. 7

Pharmacological Management

Beta-agonists and/or anticholinergic bronchodilators should be administered via the inhaled route for airflow obstruction and symptom management. 7

• Ensure patients can use inhaler devices effectively 7
• The presence of airway eosinophilia predicts better bronchodilator response to β-agonists 7
• Inflammatory cells in airways provide rationale for anti-inflammatory treatment only in select cases with airway eosinophilia or frequent exacerbations 7

Management of Acute Exacerbations

During acute exacerbations, prescribe oral corticosteroids at 30 mg per day for one week. 7

• Antibiotics are indicated if two or more of the following are present: increased breathlessness, increased sputum volume, or development of purulent sputum 7

Advanced Disease Management

Long-term oxygen therapy is the only treatment known to improve prognosis in patients with severe COPD and hypoxemia, and assessment should be conducted in a specialist setting. 7

• Pulmonary vascular remodeling accompanies medial thickening of pulmonary arterial walls secondary to hypoxia and does not resolve with long-term oxygen therapy 3
• Pulmonary hypertension in COPD is slowly progressive and implies poor prognosis 7
• Ventilatory polygraphy should be performed if clinical signs suggest obstructive sleep apnea syndrome 7

Specialized Care Requirements

Districts should ensure the following resources 7:

• A specified respiratory physician with responsibility for COPD 7
• Facilities for spirometric testing available to general practitioners 7
• Specialized respiratory nurses to liaise between hospital and primary care 7
• Resources for respiratory rehabilitation and oxygen therapy assessment 7
• Sufficient high dependency and intensive care facilities for managing respiratory failure 7

Common Pitfalls and Caveats

A critical error is failing to recognize that emphysema is a component of COPD, not a separate disease entity, though it has distinct pathophysiological and treatment implications. 1

• Do not rely solely on chest radiography for diagnosis, as it is insensitive in early disease 3
• Mucus gland thickness relates to sputum production but not to loss of respiratory function—do not confuse chronic bronchitis symptoms with emphysema severity 3
• Bronchodilator reversibility is possible even in the presence of lung pathology thought to be irreversible, so therapeutic trials are warranted 3
• DLCO helps distinguish emphysema (reduced) from pure airway disease (relatively preserved), though its value in planning treatment is less clear 7
• Current pharmacological treatments have less favorable effects in emphysematous than in non-emphysematous COPD patients 5